1,2- and 1,4-naphthoquinones: General synthesis of benzo[b]naphtho [2,3- d]furan-6,11-diones

Article abstract of DOI:10.1016/S0040-4039(00)00201-X

A new general synthesis of benzo[b]naphtho[2,3-d]furan-6,11-diones starting from readily available 2-(2'-oxo-3'-phenylpropyl)benzaldehydes is described. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00201-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2365–2367
1,2- and 1,4-Naphthoquinones: general synthesis of
benzo[b]naphtho[2,3-d]furan-6,11-diones
Ana Martínez, Juan C. Estévez, Ramón J. Estévez ∗ and Luis Castedo
Departamento de Química Orgánica and Unidade Asociada (C.S.I.C.), Universidade de Santiago,
15706 Santiago de Compostela, Spain
Received 21 December 1999; accepted 26 January 2000
Abstract
A new general synthesis of benzo[b]naphtho[2,3-d]furan-6,11-diones starting from readily available 2-(20-oxo-
30-phenylpropyl)benzaldehydes is described. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: antitumour compounds; furans; quinones; Ullmann reactions.
Naphthoquinones1 are of perennial chemical interest on account of their biological properties, their
industrial applications and their potential as intermediates in the synthesis of heterocycles such as
benzo[b]furonaphthoquinones (8)2. The latter, of known industrial interest, have recently become interes-
ting synthetic targets due to the high activity shown in various biological tests.3 We recently described two
closely related syntheses of benzofuronaphthoquinones. Both were simpler and more efficient than pre-
vious syntheses, but of limited scope because of the limited availability of the required starting materials.4
Here we report preliminary results on a more convenient synthesis of benzofuronaphthoquinones5 8 via
the corresponding 3-hydroxy-2-phenyl-1,4-naphthoquinones 10, which are easily prepared from 2-(20-
oxo-30-phenylpropyl)benzaldehydes 5 (Scheme 1).
2-(20-Oxo-30-phenylpropyl)benzaldehyde 5a was easily and efficiently obtained by aldol condensation
of 1-indanone and o-bromobenzaldehyde followed by sequential reduction and dehydration of benzylid-
eneindanone 3a and ozonolysis of the resulting indene 4a. Intramolecular aldol condensation of 5a
and subsequent dehydration of the resulting aldol produced naphthol 6a, which was easily oxidized to
the o-quinone 9a. Treatment of this latter with H2SO4 afforded 2-hydroxynaphthoquinone 10a, which
readily gave benzofuronaphthoquinone 8a when subjected to standard Ullmann coupling conditions. It
was subsequently found possible to obtain 8a more directly by oxidation of benzonaphthofuran 7a, the
product of Ullmann reaction of bromophenylnaphthol 6a.
∗
Corresponding author. Tel: +00 34 981 563100 ext. 14242; fax: +00 34 981 591014; e-mail: qorjec@uscmail.usc.es (R. J.
Estévez)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00201-X
tetl 16481

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Scheme 1. Conditions. (i) NaMeO/MeOH, rt, 15–27 h; (ii) (a) H2, Pd/C, AcOEt, 1 atm, 75–210 min; (b) NaBH4, MeOH, rt,
60–90 min; (c) H2SO4, reflux, 1–2 h; (iii) (a) O3, −78°C, 3–6 min (b) Me2S, −78°C (4–7 h), rt (13 h); (iv) NaOH aq., rt, 1.5–2
h; (v) CuO, K2CO3, pyr, reflux, 1.5–4 h (vi) Fremy’s salt, K2HPO4, acetone, rt, 1–4 h; (vii) H2SO4, MeOH, reflux, 29 h; (viii)
CrO3, AcOH, reflux, 10 min
The potential of this new synthetic route was confirmed by the successful preparation of benz-
onaphthofuran 7b and benzofuronaphthoquinone 8b from 5-methoxyindanone 1b via 2-(20-oxo-30-
phenylpropyl)benzaldehyde 5b.
To sum up, we have developed a general synthesis of benzonaphthofurans 7 and benzofuronaphthoqui-
nones 8, which is simpler and more efficient than previous syntheses, and which may have great utility
as a new simple route to 2-naphthols, naphthoquinones and other potential derivatives of 2-(20-oxo-30-
propyl)benzaldehydes 5. A systematic study of the chemistry of compounds 5, including optimization
of the new route to benzofuronaphthoquinones 8 and preparation of similar naphthoquinone compounds,
including indolenaphthoquinones, benzofluorenenaphthoquinones, is now in progress.
Acknowledgements
We thank the Spanish Ministry of Education and Culture (DGES) and the Xunta de Galicia for financial
support.
References
1. Thomson, R. H. Naturally Occurring Quinones; 4th ed.; Chapman and Hall: London, New York, 1997.
2. (a) Sartori, M. F. Chem. Rev. 1963, 63, 279–295. (b) Chatterjea, N. J.; Mehrotra, V. N. J. Indian Chem. Soc. 1963, 40,
203–212. (c) Chatterjea, N. J.; Jha, O. P. J. Indian Chem. Soc. 1970, 47, 567–575. (d) Jha, O. P. J. Indian Chem. Soc. 1973,
50, 740–742. (e) Ishikawa, S.; Takagi, M. Nippon Kagaku Kaishi 1988, 752–762. (f) Yoshida, K.; Adachi, T.; Oga, N.; Kubo,
Y. Chem. Lett. 1990, 2049–2052. (g) Yoshida, K.; Yamanaka, Y.; Ueno, Y. Chem. Lett. 1994, 2051–2054.
3. Cheng, C. C.; Dong, Q.; Liu, D.-F.; Luo, Y.-L.; Liu, L.-F.; Chen, A.-Y.; Yu, C.; Savaraj, N.; Chou, T.-C. J. Med. Chem. 1993,
36, 4108–4112.
4. Martínez, E.; Estévez, J. C., Estévez, R. J.; Castedo, L. Tetrahedron Lett. 1998, 38, 2175–2176.
5. All new compounds gave satisfactory analytical and spectroscopic data. Selected physical and spectroscopic data for
1
Compound 5a: mp, 68–69°C (methanol); IR (ν, cm−1, KBr), 1719 and 1693 (C_O); H NMR (δ, ppm), 10.01 (s, 1H,
HC_O), 7.56 (t, 1H, J=1.8 Hz, Ar-H), 7.53–7.24 (m, 7H, 7×Ar-H), 4.20 (s, 2H, -CH2-) and 4.11 (s, 2H,-CH2-). MS, m/z

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(%), 318, 316 (M+, 1), 237 (9), 147 (100). Compound 5b: mp, 87–88°C (methanol); IR (ν, cm−1, KBr), 1723 and 1684
1
(C_O); H NMR (δ, ppm), 9.76 (s, 1H, HC_O), 7.61 (d, J=8.5 Hz, 1H, Ar-H), 7.47 (d, J=7.9 Hz, 1H, Ar-H), 7.24–7.16
(m, 3H, 3×Ar-H), 6.83 (dd, J=8.5 Hz and J=2.3 Hz, 1H, Ar-H), 6.62 (d, J=2.3 Hz, 1H, Ar-H), 4.01 (s, 2H, -CH2-), 4.00 (s,
2H, -CH2-) and 3.75 (s, 3H, -OCH3). MS, m/z (%), 348, 346 (M+, 1), 267 (9), 149 (100). Compound 7a: mp, 210–212°C
(methanol); IR (ν, cm−1, KBr), 1100 (C-O-C); 1H NMR (δ, ppm), 8.42 (s, 1H, Ar-H), 8.07–7.96 (m, 3H, 3×Ar-H), 7.93 (s,
1H, Ar-H) and 7.58–7.35 (m, 5H, 5×Ar-H); MS, m/z (%), 218 (M+, 100). Compound 7b: mp, 208–210°C (methanol); IR
(ν, cm−1, KBr), 1222 (C-O-C); 1H NMR (δ, ppm), 8.30 (s, 1H, Ar-H), 8.01 (d, J=7.6 Hz, 1H, Ar-H), 7.90 (d, J=7.6 Hz, 1H,
Ar-H), 7.79 (s, 1H, Ar-H), 7.56–7.43 (m, 2H, 2×Ar-H), 7.34 (t, J=7.3 Hz, 1H, Ar-H), 7.24 (d, J=5.5 Hz, 1H, Ar-H), 7.14 (dd,
J=9.0 Hz and J=2.4 Hz, 1H, Ar-H) and 3.96 (s, 3H, -OCH3); MS, m/z (%), 248 (M+, 93), 205 (100). Compound 8a: mp,
245–247°C (methanol); IR (ν, cm−1, KBr), 1674 (C_O); 1H NMR (δ, ppm), 8.34–8.22 (m, 3H, 3×Ar-H) and 7.81–7.48 (m,
5H, 5×Ar-H); MS, m/z (%), 248 (M+, 100). Compound 8b: mp, 254–256°C (methanol); IR (ν, cm−1, KBr), 1679 (C_O);
1H NMR (δ, ppm), 8, 32 (d, J=7.5 Hz, 1H, Ar-H), 8.18 (d, J=8.6 Hz, 1H, Ar-H), 7.71–7.68 (m, 2H, 2×Ar-H), 7.61–7.50 (m,
2H, 2×Ar-H), 7.23 (s, 1H, Ar-H) and 4.00 (s, 3H, -OCH3); MS, m/z (%), 248 (M+, 3), 58 (100).